Chen Feng, Li Li, Xu Fang, Sun Yan, Du Feifei, Ma Xutao, Zhong Chenchun, Li Xiuxue, Wang Fengqing, Zhang Nating, Li Chuan
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, Shanghai, China; Hainan Medical University, Haikou, China.
Br J Pharmacol. 2013 Sep;170(2):440-57. doi: 10.1111/bph.12285.
Flavonols and terpene lactones are putatively responsible for the properties of Ginkgo biloba leaf extracts that relate to prevention and treatment of cardiovascular disease and cerebral insufficiency. Here, we characterized rat systemic and cerebral exposure to these ginkgo compounds after dosing, as well as the compounds' pharmacokinetics.
Rats received single or multiple doses of ShuXueNing injection (prepared from GBE50 for intravenous administration) or GBE50 (a standardized extract of G. biloba leaves for oral administration). Brain delivery of the ginkgo compounds was assessed with microdialysis. Various rat samples were analysed using liquid chromatography/mass spectrometry.
Slow terminal elimination features of the flavonols counterbalanced the influence of poor oral bioavailability on their systemic exposure levels, which also resulted in significant accumulation of the compounds in plasma during the subchronic treatment with ShuXueNing injection and GBE50. Unlike the flavonols, the terpene lactones had poor enterohepatic circulation due to their rapid renal excretion and unknown metabolism. The flavonol glycosides occurred as major forms in plasma after dosing with ShuXueNing injection, while the flavonol aglycone conjugates were predominant in plasma after dosing with GBE50. Cerebral exposure was negligible for the flavonols and low for the terpene lactones.
Unlike the significant systemic exposure levels, the levels of cerebral exposure to the flavonols and terpene lactones are low. The elimination kinetic differences between the two classes of ginkgo compounds influence their relative systemic exposure levels. The information gained is relevant to linking ginkgo administration to the medicinal effects.
黄酮醇和萜类内酯被认为与银杏叶提取物预防和治疗心血管疾病及脑供血不足的特性有关。在此，我们对大鼠给药后这些银杏化合物的全身和脑部暴露情况以及化合物的药代动力学进行了表征。
大鼠接受单次或多次剂量的舒血宁注射液（由银杏叶提取物50制备用于静脉注射）或银杏叶提取物50（银杏叶标准化提取物用于口服）。用微透析评估银杏化合物的脑内递送情况。使用液相色谱/质谱法分析各种大鼠样本。
黄酮醇的缓慢终末消除特征抵消了口服生物利用度差对其全身暴露水平的影响，这也导致在舒血宁注射液和银杏叶提取物50亚慢性治疗期间化合物在血浆中显著蓄积。与黄酮醇不同，萜类内酯由于其快速的肾脏排泄和未知的代谢而具有较差的肝肠循环。静脉注射舒血宁注射液给药后，黄酮醇糖苷是血浆中的主要形式，而口服银杏叶提取物50给药后，黄酮醇苷元结合物在血浆中占主导地位。黄酮醇的脑内暴露可忽略不计，萜类内酯的脑内暴露较低。
与显著的全身暴露水平不同，黄酮醇和萜类内酯的脑内暴露水平较低。两类银杏化合物之间的消除动力学差异影响它们的相对全身暴露水平。所获得的信息与将银杏给药与药用效果联系起来相关。
